A breast cancer investigation is usually triggered by the discovery of a breast mass, and although in many instances the mass is the result of a benign lesion, this is not discovered until a patient has often undergone a battery of diagnostic tests which are sometimes invasive. A need exists for a noninvasive, adjunctive method and device which will aid a physician in making a clinical decision as to whether or not additional diagnostic tests for breast cancer are warranted.
Breast cancer is thought to originate from epithelial cells in the terminal ductal lobular units of mammary tissue. The development of breast cancer results in regions of epithelial electrical depolarization within the breast parenchyma, which led to the theory that the measurement of skin surface electropotentials would provide data to indicate the presence of underlying abnormal proliferation indicative of cancer. Many methods and devices have been developed in an attempt to implement this theory.
For example, U.S. Pat. No. 4,328,809 to B. H. Hirschowitz et al. deals with a device and method for detecting the potential level of the electromagnetic field present between a reference point and a test point on a living organism. Here, a reference electrode provides a first signal indicative of the potential level of the electromagnetic field at the reference point, while a test electrode provides a second signal indicative of the potential level of the electromagnetic field at the test point. These signals are provided to an analog-to-digital converter which generates a digital signal as a function of the potential difference between the two, and a processor provides an output signal indicative of a parameter or parameters of the living organism as a function of this digital signal. For breast cancer detection, Hirschowitz et al. shows that a test electrode can be placed in each quadrant of a human female breast and that multiple measurements can be taken during a test period with each test electrode and a reference electrode. These multiple measurements are digitized, normalized, and summed to provide an average or mean output signal indicative of a parameter of the living organism under test.
Similar biopotential measuring devices are shown by U.S. Pat. No. 4,407,300 to Davis, and U.S. Pat. No. 4,557,271 and 4,557,273 to Stoller et al. Davis in particular discloses the diagnosis of cancer by measuring the electromotive forces generated between two electrodes applied to a subject.
Often, the measurement of biopotentials has been accomplished using an electrode array, with some type of multiplexing system to switch between electrodes in the array. The aforementioned Hirschowitz et al. patent contemplates the use of a plurality of test electrodes, while U.S. Pat. No. 4,416,288 to Freeman and U.S. Pat. No. 4,486,835 to Bai disclose the use of measuring electrode arrays.
Unfortunately, these previous methods for employing biopotentials measured at the surface of a living organism as an adjunctive aid to diagnosis, while basically valid, are predicated upon an overly simplistic hypothesis which is not effective for many disease states. The prior methods and devices which implement them operate on the basis that a disease state is indicated by a negative polarity which occurs relative to a reference voltage obtained from another site on the body of a patient, while normal or non-malignant states, in the case of cancer, are indicated by a positive polarity. Based upon this hypothesis, it follows that the detection of disease states can be accomplished by using one measuring electrode situated externally on or near the disease site to provide a measurement of the polarity of the signal received from the site relative to that from the reference site. Where multiple measuring electrodes have been used, their outputs have merely been summed and averaged to obtain one average signal from which a polarity determination is made. This approach can be subject to major deficiencies which lead to inaccuracy, particularly where only surface measurements are taken.
U.S. Pat. Nos. 4,955,383 and 5,099,844 to M. L. Faupel disclose a method and apparatus using electropotential differentials between averaged values provided by a plurality of different sensors. This method operates on the basis that maximum differentials between areas of diseased tissue and apparently normal tissue in other areas of a breast for a breast cancer investigation provide informative parameters not subject to the inaccuracy of previous methods.
Still, the accurate measurement of DC biopotentials for sensing disease, such as breast cancer, is very difficult to accomplish, for the DC potentials to be sensed are of a very low amplitude. Due to factors such as the low DC potentials involved and the innate complexity of biological systems, the collected data signals tend to include a substantial amount of noise which makes accurate analysis difficult. Also, biological systems are notorious for their complexity, nonlinearity and nonpredictability, and wide variations from the norm are not uncommon. Thus it is necessary to develop a method and apparatus for obtaining the necessary data from the measurement of biopotentials and then to extract and analyze pertinent information which is relevant to a condition under study.
In an attempt to accomplish this, the method and apparatus of the previous Faupel patents was combined with one or more preprogrammed neural networks as illustrated by U.S. Pat. No. 5,697,369 to D. M. Long Jr et al. and U.S. Pat. No. 5,715,821 to M. L. Faupel. With a neural network, data can be processed by several layers of interacting decision points or neurons. The network must be taught to recognize patterns from input data to produce a predictive output, and this can prove to be a complex and often time consuming process involving many variables. Therefore, a need has arisen for a simple method and apparatus for use in the analysis of female breast electropotentials to minimize the effects of noise on the measurement data and to compensate for the biologic variability which affects the measurement data. Past methods and devices have concentrated on developing accurate data from sensed biopotentials which will provide an indication of the probability that a malignancy exists. These methods have ignored the effects of various biologic variables such as menstrual status or timing of the menstrual cycle. (Electrical Potential Measurements in Human Breast Cancer and Benign Lesions; Tumor Biology, 1994, pages 147-152). However, in younger women (ages 18-56) with a palpable breast mass, the prevalence of cancer becomes lower as age decreases. The sensitivity of mammography is limited in this less than 56 age group due to the density of breast tissue. Because of this, a considerable degree of diagnostic uncertainty remains after physical examination and mammography, and as a result, the open biopsy procedure performed on women in this 56 year or under population yields a low percentage of malignancy diagnoses. Physicians dealing with breast cancer detection have a need for a noninvasive technique which will provide data to effectively aid them in reaching a clinical decision that a suspicious lesion is benign and does not require a breast biopsy while still providing an indication that malignancy is probable when such is the case so that a decision can be made to conduct a biopsy.
It is a primary object of the present invention to provide a novel and improved method and apparatus for sensing and processing electropotentials from a female breast which minimizes the effects of noise on the measurement data.
Another object of the present invention is to provide a novel and improved method and apparatus for sensing and processing electropotentials from a human subject which involves weighting the measured electropotentials to compensate for biologic variables.
A further object of the present invention is to provide a novel and improved method and apparatus for sensing and processing electropotentials from a human subject which involves weighting the measured electropotentials in accordance with the age of the subject.
Yet another object of the present invention is to provide a novel and improved method and apparatus for sensing and processing electropotentials from a female breast which involves weighting and/or discarding the electropotential measurement in response to the dates of menses and/or hormonal levels.
A further object of the present invention is to provide a novel and improved method and apparatus for sensing and processing electropotentials from a female breast where a primary electropotential measurement is obtained from an area of a symptomatic breast which is directly over a lesion and this primary electropotential measurement is processed with an electropotential measurement obtained from one or more areas of the symptomatic breast which are spaced from the lesion to provide noise reduction.
Yet a further object of the present invention is to provide a novel and improved method and apparatus for sensing and processing electropotentials from a female breast where a primary electropotential measurement is obtained from an area of a symptomatic breast which is directly over a lesion and this primary electropotential measurement is processed with electropotential measurements obtained from one or more areas of the symptomatic breast which are spaced from the lesion and from areas of the asymptomatic breast which correspond with the areas of the symptomatic breast where measurements are taken to reduce noise.
Another object of the present invention is to provide a novel and improved method and apparatus for sensing and processing electropotentials from a female breast which involves weighting the measured electropotentials to compensate for biologic variables which include one or more of patient age, hormonal levels, time in the patient menstrual cycle, and time of day during which the measurement is taken.
These and other objects of the present invention are accomplished by the apparatus and method of the present invention. In the most basic mode of operation, a biopotential sensor is placed directly over a lesion in a symptomatic breast, a reference sensor is located either away from the symptomatic breast, or directly over the nipple of the symptomatic breast, and a plurality of electropotential test measurements are taken during a test period and averaged to obtain a primary test potential. This primary test potential can be weighted to compensate for one or more biologic variables such as patient age, hormonal levels, time in the patient menstrual cycle, and the time of day during which the measurement is taken. These biologic variables are provided to a processor for the apparatus by one or more data input devices which can include a keyboard and possibly sensors for some biologic conditions. The processor stores weighting factors for each biologic variable and various levels of the biologic variable, and applies one or more of these weighting factors to the primary test potential measurement which is then displayed or compared to a reference value and the result displayed. For some period of a female menstrual cycle, the processor will either prevent the display and will instead provide an indication that no accurate measurement can be taken, or will weight the measurement taken to compensate for the period during the menstrual cycle when the measurement is obtained.
To provide noise enhancement of the primary test potential average measurement, the symptomatic breast is divided into four equal quadrants with one quadrant containing the lesion. At least one of the remaining three non-lesion quadrants is provided with a biopotential sensor, and during the test period a number of electropotential measurements equal to those taken by the sensor over the lesion are taken and averaged. This average value from the non-lesion quadrant is subtracted from the primary test potential average to provide a differential value which then can be compared to a predetermined reference value and the result displayed. Often both the average from the non-lesion quadrant and the primary test potential average are weighted before the subtraction step by the processor to obtain the differential. Also, the processor will often provide additional weighting for biologic variables.
Further enhanced noise reduction of the primary test potential average measurement is obtained by placing at least one biopotential sensor in each non-lesion quadrant of the breast and taking the same number of electropotential test measurements during a test period from each non-lesion quadrant that are taken with the sensor over the lesion. At the end of the test period, the processor averages the measurements taken by each sensor to obtain an average, and the average for the sensor over the lesion constitutes the primary test potential. The processor may then obtain the median value of the averages for the non-lesion quadrants or alternatively the mean value, and it will then subtract this median or mean value from the primary test potential to provide the differential value. Again the mean or median value and the primary test potential may be weighted before the subtraction and additional weighting may be provided for biologic variables. The resultant differential value is then compared to a predetermined reference value.
Maximum noise reduction of the primary test potential average is obtained as described above using averages obtained from the biopotential sensors over the non-lesion quadrants of the symptomatic breast. Also mirror image sensors are arranged on the asymptomatic breast to duplicate the positions of the sensors on the symptomatic breast. During a test period, the processor causes all sensors to take the same number of plural electropotential measurements, and at the end of the test period the average value of the measurements for each individual channel is computed.
For the symptomatic breast, the processor computes either the median or the mean value for the non-lesion quadrants. For the asymptomatic breast, the processor computes a maximum voltage differential value (MVD) which is the difference value obtained by subtracting the lowest average value obtained for the asymptomatic breast from the highest average value. Then the processor subtracts the median or mean value for the non-lesion quadrants of the symptomatic breast from the primary test potential average and adds the MVD from the asymptomatic breast to obtain a differential value which is compared to a predetermined reference.
Alternatively, instead of the MVD from the asymptomatic breast, the processor may obtain a median value or a mean value from the averages for the asymptomatic breast and add these to the result of the subtraction of values for the symptomatic breast. Again, all values from the symptomatic and asymptomatic breast may be weighted and additional weighting may be provided for biologic variables.
For screening purposes, at least one sensor may be placed in each breast quadrant and multiple measurements taken with each sensor and averaged to obtain a quadrant average value for each quadrant. The average values are compared, and if a quadrant average value varies from the others by more than a predetermined amount, this quadrant is designated as a potential lesion quadrant.